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- W2912120675 abstract "The dendritic network of actin filaments provides the force for lamellipodial protrusions, driven by actin filament polymerization and branch generation by the Arp2/3 complex. Electron microscopy experiments of lamellipodia revealed that the network structure of filaments varies with distance to the leading edge. Near the leading edge there is a dense brushwork composed of short filaments. Filaments are longer and appear more linear near the center and rear of keratocyte lamellipodia. Prior modeling of FRAP and single molecule imaging experiments suggested the existence of a diffuse actin oligomer cytoplasmic pool and distributed turnover of F-actin through the lamellipodium. The precise mechanisms behind network remodeling and the role of the oligomer pool have yet to be determined. To answer this question, we created a three-dimensional stochastic model at the filament level that includes rate constants for known mechanisms of polymerization, depolymerization, branching, capping, uncapping, severing and debranching. The model reproduces the +/− 35o orientation pattern when branching occurs within 10o of the lamellipodial plane as well as the density of branches, ends and length distribution near the leading edge for both fibroblast and keratocyte lamellipodia (that differ in the magnitude of retrograde flow and polymerization rates). We show that the simplest implementations of severing, debranching, uncapping, and depolymerization from either pointed or barbed ends does not provide mechanisms for network structural remodeling at the level observed in electron micrographs. We examine and test several mechanisms that include severing and oligomer annealing that may provide an explanation." @default.
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- W2912120675 date "2019-02-01" @default.
- W2912120675 modified "2023-09-30" @default.
- W2912120675 title "Mechanisms for Dendritic Actin Network Formation, Distributed Turnover, and Structural Remodeling" @default.
- W2912120675 doi "https://doi.org/10.1016/j.bpj.2018.11.2463" @default.
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